Long-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study
Authors: Michael R. Rickels, Thomas L. Eggerman, Levent Bayman, Julie C. Qidwai, Rodolfo Alejandro, Nancy D. Bridges, Bernhard J. Hering, James F. Markmann, Peter A. Senior, Lawrence G. Hunsicker, Jose Avila, Beth Begley, Jose Cano, Sallie Carpentier, Elizabeth Holbrook, Jennifer Hutchinson, Christian P. Larsen, Johanna Moreno, Marti Sears, Nicole A. Turgeon, Dasia Webster, Christian Berne, Carl Jorns, Torbjörn Lundgren, Mikael Rydén, Enrico Cagliero, Kerry Crisalli, S. Deng, Ji Lei, James F. Markmann, David Nathan, Patrice Al-Saden, Jason Battle, Xioajuan Chen, Angela Hecyk, Dixon B. Kaufman, Herman Kissler, Xunrong Luo, Mark Molitch, Natalie Monson, Elyse Stuart, Amisha Wallia, Lingjia Wang, Shusen Wang, Xiaomin Zhang, Nancy D. Bridges, Christine W. Czarniecki, Julia S. Goldstein, Tomeka Granderson, Yvonne Morrison, Allison Priore, Gerry Putz, Mark A. Robien, Elizabeth Schneider, Guillermo Arreaza, Thomas L. Eggerman, Neal Green, David L. Bigam, Patricia Campbell, Parastoo Dinyari, Sharleen Imes, Tatsuya Kin, Norman M. Kneteman, Angela Koh, James Lyon, Andrew Malcolm, Doug O’Gorman, Chris Onderka, Richard Owen, Rena Pawlick, Brad Richer, Shawn Rosichuk, Edmond A. Ryan, Donna Sarman, Adam Schroeder, Peter A. Senior, A.M. James Shapiro, Lana Toth, Vali Toth, Wendy Zhai, Kristina Johnson, Joan McElroy, Andrew M. Posselt, Marissa Ramos, Tara Rojas, Peter G. Stock, Gregory Szot, Barbara Barbaro, Leelama George, Joan Martellotto, Jose Oberholzer, Meirigeng Qi, Yong Wang, Levent Bayman, Kathryn Chaloner, William R. Clarke, Joseph S. Dillon, Cynthia Diltz, Gregory C. Doelle, Dixie Ecklund, Holly Ernst, Deb Feddersen, Eric Foster, Lawrence G. Hunsicker, Carol Jasperson, David-Erick Lafontant, Karen McElvany, Tina Neill-Hudson, Deb Nollen, Julie Qidwai, Traci Schwieger, Beth Shields, Jamie Willits, Jon Yankey, Rodolfo Alejandro, A. Alvarez, Andrea Curry Corrales, Raquel Faradji, Tatiana Froud, Ana Alvarez Gil, Eva Herrada, H. Ichii, Luca Inverardi, Norma Kenyon, Aisha Khan, Elina Linetsky, J. Montelongo, Eduardo Peixoto, K. Peterson, Camillo Ricordi, J. Szust, X. Wang, Xiumin Xu, Muhamad H. Abdulla, J. Ansite, A.N. Balamurugan, Melena D. Bellin, Mary Brandenburg, T. Gilmore, James V. Harmon, Bernhard J. Hering, Raja Kandaswamy, Gopal Loganathan, Kate Mueller, Klearchos K. Papas, Jayne Pedersen, Joshua J. Wilhelm, Jean Witson, Aksel Foss, Trond Jenssen, Cornelia Dalton-Bakes, Hongxing Fu, Malek Kamoun, Jane Kearns, Yanjing Li, Chengyang Liu, Eline Luning-Prak, Yanping Luo, Eileen Markmann, Zaw Min, Ali Naji, Maral Palanjian, Michael R. Rickels, Richard Shlansky-Goldberg, Kumar Vivek, Amin Sam Ziaie, Peter Chebleck, Juan Sebastian Danobeitia, Luis Fernandez Dixon B. Kaufman, Jon Odorico, Kristi Schneider, Laura Zitur, D. Brandhorst, A. Friiberg, Olle Korsgren, Bo Nilsson, Gunnar Tufveson, Bengt von Zur-MΈhlen, Irene Feurer
Journal: Diabetes Care (2022)

OBJECTIVE To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia. RESEARCH DESIGN AND METHODS This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c &amp;lt;7.0%), freedom from severe hypoglycemia, and insulin independence. RESULTS Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c &amp;lt;7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at &amp;gt;90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation. CONCLUSIONS Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.